Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine.

Kobayashi T, Washiyama K, Ikeda K.
Atomoxetine and reboxetine are commonly used as selective norepinephrine reuptake inhibitors (NRIs) for the treatment of attention-deficit-hyperactivity disorder and depression, respectively. Furthermore, recent studies have suggested that NRIs may be useful for the treatment of several other psychiatric disorders. However, the molecular mechanisms underlying the various effects of NRIs have not . . . → Read More: Inhibition of G-protein-activated inwardly rectifying K+ channels by the selective norepinephrine reuptake inhibitors atomoxetine and reboxetine.

Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine.

Salvadore G, Cornwell BR, Sambataro F, Latov D, Colon-Rosario V, Carver F, Holroyd T, DiazGranados N, Machado-Vieira R, Grillon C, Drevets WC, Zarate CA Jr.
Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl-D-aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in . . . → Read More: Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine.

White matter integrity is associated with treatment outcome measures in cocaine dependence.

Xu J, DeVito EE, Worhunsky PD, Carroll KM, Rounsaville BJ, Potenza MN.
Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users’ abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine . . . → Read More: White matter integrity is associated with treatment outcome measures in cocaine dependence.

Abnormal mGlu 5 receptor-endocannabinoid coupling in mice lacking FMRP and BC1 RNA.

Maccarrone M, Rossi S, Bari M, De Chiara V, Rapino C, Musella A, Bernardi G, Bagni C, Centonze D.
Transcriptional silencing of the gene encoding the fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS). FMRP acts as a translational repressor at central synapses, and molecular and synaptic plasticity studies have shown that the absence . . . → Read More: Abnormal mGlu 5 receptor-endocannabinoid coupling in mice lacking FMRP and BC1 RNA.

Altered neural cholinergic receptor systems in cocaine-addicted subjects.

Adinoff B, Devous MD Sr, Williams MJ, Best SE, Harris TS, Minhajuddin A, Zielinski T, Cullum M.
Changes in the brain’s cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer’s disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study . . . → Read More: Altered neural cholinergic receptor systems in cocaine-addicted subjects.

Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers.

Petrovsky N, Quednow BB, Ettinger U, Schmechtig A, M?ssner R, Collier DA, K?hn KU, Maier W, Wagner M, Kumari V.
Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine . . . → Read More: Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers.

Rosiglitazone rescues memory impairment in Alzheimer’s transgenic mice: mechanisms involving a reduced amyloid and tau pathology.

Escribano L, Sim?n AM, Gimeno E, Cuadrado-Tejedor M, de Maturana RL, Garc?a-Osta A, Ricobaraza A, P?rez-Mediavilla A, R?o JD, Frechilla D.
Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARgamma) may exert beneficial effects in patients with mild-to-moderate Alzheimer’s disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs . . . → Read More: Rosiglitazone rescues memory impairment in Alzheimer’s transgenic mice: mechanisms involving a reduced amyloid and tau pathology.

Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis.

Maayan L, Vakhrusheva J, Correll CU.
Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of Science, PsycNET, and EMBASE for randomized, open and double-blind, placebo-controlled trials of medications targeting antipsychotic-induced weight gain was performed. Primary outcome measures were change and endpoint values in . . . → Read More: Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis.

Contrasting effects of increased and decreased dopamine transmission on latent inhibition in ovariectomized rats and their modulation by 17beta-estradiol: an animal model of menopausal psychosis?

Arad M, Weiner I.
Women with schizophrenia have later onset and better response to antipsychotic drugs (APDs) than men during reproductive years, but the menopausal period is associated with increased symptom severity and reduced treatment response. Estrogen replacement therapy has been suggested as beneficial but clinical data are inconsistent. Latent inhibition (LI), the capacity to ignore irrelevant . . . → Read More: Contrasting effects of increased and decreased dopamine transmission on latent inhibition in ovariectomized rats and their modulation by 17beta-estradiol: an animal model of menopausal psychosis?

Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity.

Chen CC, Yang CH, Huang CC, Hsu KS.
The mossy fiber synapses onto hippocampal CA3 neurons show unique molecular features and a wide dynamic range of plasticity. Although acute stress has been well recognized to alter bidirectional long-term synaptic plasticity in the hippocampal CA1 region and dentate gyrus, it remains unclear whether the same effect may also . . . → Read More: Acute stress impairs hippocampal mossy fiber-CA3 long-term potentiation by enhancing cAMP-specific phosphodiesterase 4 activity.

Gender-specific association of galanin polymorphisms with HPA-axis dysregulation, symptom severity, and antidepressant treatment response.

Unschuld PG, Ising M, Roeske D, Erhardt A, Specht M, Kloiber S, Uhr M, M?ller-Myhsok B, Holsboer F, Binder EB.
Galanin (GAL) is an estrogen-inducible neuropeptide, highly expressed in brain regions reported to be involved in regulation of mood and anxiety. GAL possibly has a direct modulatory effect on hypothalamic-pituitary-adrenal (HPA)-axis regulation. Recent data from pharmacological and . . . → Read More: Gender-specific association of galanin polymorphisms with HPA-axis dysregulation, symptom severity, and antidepressant treatment response.

Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning.

Ito R, Canseliet M.
Behaviorally sensitizing regimen of amphetamine (AMPH) exposure has diverse effects on learning, memory, and cognition that are likely to be a consequence of long-term neural adaptations occurring in the cortico-limbic-striatal circuitry. In particular, altered dopamine signaling in the nucleus accumbens and medial prefrontal cortex has been implicated to underlie AMPH-induced changes in . . . → Read More: Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning.

Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat.

Axel AM, Mikkelsen JD, Hansen HH.
Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management is not clarified. Using a rat model of diet-induced obesity (DIO), we . . . → Read More: Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat.

Adenosine A1 receptors and microglial cells mediate CX3CL1-induced protection of hippocampal neurons against Glu-induced death.

Lauro C, Cipriani R, Catalano M, Trettel F, Chece G, Brusadin V, Antonilli L, van Rooijen N, Eusebi F, Fredholm BB, Limatola C.
Fractalkine-CX3CL1 is a neuron-associated chemokine, which modulates microglia-induced neurotoxicity activating the specific and unique receptor CX3CR1. CX3CL1-CX3CR1 interaction modulates the release of cytokines from microglia, reducing the level of tumor necrosis factor-alpha, interleukin-1-beta, and . . . → Read More: Adenosine A1 receptors and microglial cells mediate CX3CL1-induced protection of hippocampal neurons against Glu-induced death.

Evidence of altered polyamine concentrations in cerebral cortex of suicide completers.

Chen GG, Fiori LM, Moquin L, Gratton A, Mamer O, Mechawar N, Turecki G.
Recent studies have implicated alterations in the expression of polyamine-related genes in the brains of suicide completers including widespread downregulation of spermidine-spermine N1-acetyltransferase, the key enzyme in polyamine catabolism, suggesting compensatory mechanisms attempting to increase brain levels of polyamines. Given the complexity . . . → Read More: Evidence of altered polyamine concentrations in cerebral cortex of suicide completers.

Impact of lipid raft integrity on 5-HT3 receptor function and its modulation by antidepressants.

Nothdurfter C, Tanasic S, Di Benedetto B, Rammes G, Wagner EM, Kirmeier T, Ganal V, Kessler JS, Rein T, Holsboer F, Rupprecht R.
Because of the biochemical colocalization of the 5-HT(3) receptor and antidepressants within raft-like domains and their antagonistic effects at this ligand-gated ion channel, we investigated the impact of lipid raft integrity for . . . → Read More: Impact of lipid raft integrity on 5-HT3 receptor function and its modulation by antidepressants.

Long-Evans rats acquire operant self-administration of 20% ethanol without sucrose fading.

Simms JA, Bito-Onon JJ, Chatterjee S, Bartlett SE.
A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume . . . → Read More: Long-Evans rats acquire operant self-administration of 20% ethanol without sucrose fading.

TrkB-BDNF-dependent striatal plasticity and behavior in a genetic model of epilepsy: modulation by valproic acid.

Ghiglieri V, Sgobio C, Patassini S, Bagetta V, Fejtova A, Giamp? C, Marinucci S, Heyden A, Gundelfinger ED, Fusco FR, Calabresi P, Picconi B.
In mice lacking the central domain of the presynaptic scaffold Bassoon the occurrence of repeated cortical seizures induces cell-type-specific plasticity changes resulting in a general enhancement of the feedforward inhibition within the . . . → Read More: TrkB-BDNF-dependent striatal plasticity and behavior in a genetic model of epilepsy: modulation by valproic acid.

The expression of VGF is reduced in leukocytes of depressed patients and it is restored by effective antidepressant treatment.

Cattaneo A, Sesta A, Calabrese F, Nielsen G, Riva MA, Gennarelli M.
Major depression is a disease characterized by an inability of neuronal systems to show appropriate adaptive plasticity especially under challenging conditions, such as stress. Conversely, pharmacological intervention may normalize such defects through the modulation of factors that might act in concert for the functional . . . → Read More: The expression of VGF is reduced in leukocytes of depressed patients and it is restored by effective antidepressant treatment.